Impact of PD-L1 and <i>KRAS</i> status on the efficacy of nintedanib (NIN) + docetaxel (DOC) following treatment with first-line immune checkpoint inhibitor (ICI) + chemotherapy in patients with adenocarcinoma NSCLC: Analysis of cohort C of the non-interventional VARGADO trial.
Authors: Christian Grohé, Thomas Wehler, Sven Henschke, Stefan Hammerschmidt, Christoph Aulmann, Stefan Krüger, Ina Dittrich, Wolfgang Schuette, Eyck von der Heyde, Sven Hanson, Joerg Bajorat, Rolf Kaiser
Journal: Journal of Clinical Oncology (2023)

e21149 Background: The identification of targetable molecular tumor markers in patients (pts) with NSCLC has increased significantly over the past decades and has resulted in important changes to individual treatment approaches. One such marker is KRAS G12C for which a specific treatment is now available following prior systemic therapy. While ICIs ± chemotherapy represent first-line (1L) standard of care, the sequence of subsequent effective therapies still needs to be investigated. Methods: Cohort C of the ongoing, prospective, non-interventional VARGADO study (NCT02392455) is investigating the combination of NIN + DOC as second-line (2L) treatment after prior 1L ICI + chemotherapy in pts with adenocarcinoma NSCLC. This updated analysis of Cohort C focuses on the safety and efficacy of NIN + DOC according to programmed death ligand-1 (PD-L1) and KRAS status. Results: At the cut-off date (December 1, 2022) 219 pts have been enrolled to Cohort C. Median age was 64 years (range: 37–84) and 58.9% (129/219) of pts were men. At baseline, 30.6% (67/219) were ECOG PS 0 and 50.2% (110/219) were ECOG PS 1. 88.1% (193/219) had stage IV disease. Brain metastases were present in 19.2% (42/219) of pts and 88.1% (193/219) had received prior 1L pembrolizumab-based combination therapy. In the overall population, median PFS was 4.5 months (mo; 95% CI: 3.6–5.3, 219 pts) and median OS was 9.6 mo (95% CI: 6.5–11.2, 217 pts) with NIN + DOC. KRAS mutation status has been documented for 119 pts. In KRAS wild-type pts (75/119), median PFS was 3.7 mo (95% CI: 2.6–5.3) and median OS was 7.7 mo (95% CI: 5.2-11.2). In KRAS mutation-positive pts (44/119) median PFS was 5.1 mo (95% CI: 3.4–6.3) and median OS was 6.7 mo (95% CI: 5.3–15.1). In 33 pts with a non-G12C KRAS mutation, median PFS was 5.0 mo (95% CI: 3.4–6.7) and median OS was 6.7 mo (95% CI: 5.3–15.1). ORR was 20.0% (15/75), 25.0% (11/44), 27.3% (9/33) and 18.2% (2/11) in pts with KRAS wild-type, KRAS mutated, non-G12C mutated and G12C mutated status, respectively. The corresponding disease control rates (DCR) were 45.3% (34/75), 47.7% (21/44), 48.5% (16/33) and 45.5% (5/11). PD-L1 status prior to 1L therapy was &lt; 1% in 86 pts and ≥1% in 76 pts and did not impact OS (median 10.6 mo [95% CI: 6.5–15.1] and 10.5 mo [95% CI: 5.7–12.5], respectively) or DCR (51.2% and 51.3%, respectively) with NIN + DOC. The most frequent NIN-related adverse events of any grade in the overall population were diarrhea 34.7% (76/219), nausea 14.2% (31/219), vomiting 8.2% (18/219) and fatigue 7.8% (17/219). Conclusions: NIN + DOC is an effective and safe 2L treatment option after prior 1L ICI + chemotherapy for NSCLC adenocarcinoma pts independent of PD-L1 and KRAS status. Clinical trial information: NCT02392455 .